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AutorMelo, Mariane B.
AutorKasperkovitz, Pia
AutorCerny, Anna
AutorKonen Waisman, Stephanie
AutorJones, Evelyn A. Kurt
AutorLien, Egil
AutorBeutler, Bruce
AutorHoward, Jonathan C.
AutorGolenbock, Douglas Taylor
AutorGazzinelli, Ricardo Tostes
Fecha de acceso2012-11-27T15:33:08Z
Fecha de disponibilización2012-11-27T15:33:08Z
Fecha de publicación2010
ReferenciaMELO, Mariane B, et al. (2010) UNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondii. PLoS Pathog 6(8): e1001071.pt_BR
ISSN15537366
URIhttps://www.arca.fiocruz.br/handle/icict/5878
PromociónNational Institutes of Health, National Institute of Science and Technology for Vaccines/CNPqpt_BR
Idiomaengpt_BR
EditorPublic Library of Science (PLoS)pt_BR
Derechos de autoropen accesspt_BR
TítuloUNC93B1 Mediates Host Resistance to Infection with Toxoplasma gondiipt_BR
Tipo del documentoArticlept_BR
DOI10.1371/journal.ppat.1001071
Resumen en InglésUNC93B1 associates with Toll-Like Receptor (TLR) 3, TLR7 and TLR9, mediating their translocation from the endoplasmic reticulum to the endolysosome, hence allowing proper activation by nucleic acid ligands. We found that the triple deficient ‘3d’ mice, which lack functional UNC93B1, are hyper-susceptible to infection with Toxoplasma gondii. We established that while mounting a normal systemic pro-inflammatory response, i.e. producing abundant MCP-1, IL-6, TNFa and IFNc, the 3d mice were unable to control parasite replication. Nevertheless, infection of reciprocal bone marrow chimeras between wildtype and 3d mice with T. gondii demonstrated a primary role of hemopoietic cell lineages in the enhanced susceptibility of UNC93B1 mutant mice. The protective role mediated by UNC93B1 to T. gondii infection was associated with impaired IL-12 responses and delayed IFNc by spleen cells. Notably, in macrophages infected with T. gondii, UNC93B1 accumulates on the parasitophorous vacuole. Furthermore, upon in vitro infection the rate of tachyzoite replication was enhanced in nonactivated macrophages carrying mutant UNC93B1 as compared to wild type gene. Strikingly, the role of UNC93B1 on intracellular parasite growth appears to be independent of TLR function. Altogether, our results reveal a critical role for UNC93B1 on induction of IL-12/IFNc production as well as autonomous control of Toxoplasma replication by macrophages.pt_BR
AfiliaciónUniversity of Massachusetts Medical School. Worcester, MA, United States of Americapt_BR
AfiliaciónUniversity of Massachusetts Medical School. Worcester, MA, United States of Americapt_BR
AfiliaciónUniversity of Massachusetts Medical School. Worcester, MA, United States of Americapt_BR
AfiliaciónInstitute for Genetics, University of Cologne. Cologne, Germanypt_BR
AfiliaciónUniversity of Massachusetts Medical School. Worcester, MA, United States of Americapt_BR
AfiliaciónUniversity of Massachusetts Medical School. Worcester, MA, United States of Americapt_BR
AfiliaciónScripps Research Institute. La Jolla, CA, United States of Americapt_BR
AfiliaciónInstitute for Genetics, University of Cologne. Cologne, Germanypt_BR
AfiliaciónUniversity of Massachusetts Medical School. Worcester, MA, United States of America/ Fundacão Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazilpt_BR
AfiliaciónUniversity of Massachusetts Medical School. Worcester, MA, United States of America , Fundacão Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, Brazil/ Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazilpt_BR
Palavras clave en InglêsToxoplasma gondiipt_BR
Palavras clave en InglêsResistance to Infectionpt_BR


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